Influence of Cysteinate Protonation on Biologically Relevant Nickel-Mediated Reactions

在这项由美国国家科学基金会化学部化学结构、动力学和机制B计划资助的项目中，内华达大学雷诺分校化学系的Jason Sheeller教授正在研究质子化硫配体对金属酶活性部位的影响。近年来，这种结构在一些金属蛋白活性部位被认为是重要的，但它对结构和催化作用的影响还没有得到很好的研究。该项目研究了一些定义明确的合成镍硫化合物，并评估了它们的反应性、结构和性能。这项研究对许多催化系统的设计和生产产生了影响，包括那些在清洁能源、日用化学品和制药方面很重要的催化系统。此外，该项目还为培训科学、技术、教育和数学(STEM)领域的高技能工人提供了一个教育平台。半胱氨酸连接的金属酶代表着一种不同类别的生物分子，涉及从电子转移到碳氢化合物官能化的反应。最近，人们发现镍铁氢酶的活性中心含有一个质子化的配位镍硫键。这增加了少量但不断增加的酶系统，如包含这种结构元素的镍超氧化物歧化酶。该研究小组最近发现，这一特征不仅在调节镍-硫酸盐连接体系的结构和性质方面很重要，而且还可以参与质子耦合电子转移反应等反应。这项研究试图了解设计的含镍小分子和含有质子化镍-硫键的金属多肽体系的性质和反应性。为了理解这些体系，进行了一系列的光谱、计算、反应性和机理研究。通过这些研究获得的信息被用于合理地设计具有微调的电子和几何结构属性的系统，这些系统可以对目标底物执行特定的反应。

In this project funded by the Chemical Structure, Dynamics and Mechanisms B Program of the Chemistry Division of the NSF, Professor Jason Shearer of the Department of Chemistry at University of Nevada, Reno is studying the influence of protonated sulfur ligands at the active sites of metalloenzymes. This type of structure has recently been recognized as important in several metalloprotein active sites, yet its impact on structure and catalysis has not been well studied. This project examines a number of well-defined synthetic nickel-sulfur compounds and evaluates their reactivity, structure and properties. The research has impacts on the design and production of a number of catalytic systems, including those important in clean energy, commodity chemical, and pharmaceuticals. In addition, the project provides an educational platform for the training of highly skilled workers in a number of Science, Technology, Education and Mathematics (STEM) fields.Cysteinate-ligated metalloenzymes represent a diverse class of biomolecules that are involved in reactions ranging from electron transfer to hydrocarbon functionalization. Recently, it was discovered that the active site of nickel-iron hydrogenase contains a protonated-coordinated nickel-sulfur bond. This adds to a small, but growing number of enzymatic systems, such as nickel superoxide dismutase that contain this structural element. This research group has recently shown that this feature is not only important in modulating the structure and properties of nickel-thiolate ligated systems, but can also be involved in reactions such as proton coupled electron transfer reactions. This research seeks to understand the properties and reactivities of designed nickel containing small molecules and metallopeptide-based systems that contain the protonated nickel-sulfur bond. A series of spectroscopic, computational, reactivity, and mechanistic studies are undertaken to understand these systems. Information learned through these studies is used to rationally design systems with fine-tuned electronic and geometric structural properties that can perform specific reactions towards targeted substrates.